Zoledronic acid (I) is a bisphosphonic acid, which acts as an inhibitor of bone osteoclastic resorption. This compound, chemically called 1-hydroxy-2-(1-imidazoyl)ethydilene bisphosphonic acid, is sold in the USA under the trade name of Zometa® (zoledronic acid for injectables).
Zoledronic acid belongs to the family of the bisphosphonates well known for its features useful when treating diseases caused by dysfunctions in the metabolism of calcium and phosphorous [see for example K. R. Williams-J. C'hem. Ed. 81, 1406 (2004)].
There exist several patents describing methods for the obtention of bisphosphonates, particularly for zoledronic acid and its salts. DE 3626058 (1988); U.S. Pat. No. 4,777,163 (1988); EP 258618 (1988); U.S. Pat. No. 4,939,130 (1990) could be mentioned.
In Chemical Abstract Services, there are various forms of free zoledronic acid and its salts registered:
1. Anhydrous Zoledronic acid (RN: 118072-93-8).
2. Monohydrate Zoledronic acid (RN:165800-06-6).
3. Zoledronic Acid, anhydrous disodium salt (RN: 131654-46-1).
4. Zoledronic Acid, monohydrate disodium salt (RN: 165800-07-7)
5. Zoledronic Acid, monohydrate trisodium salt (RN: 165 800-08-8).
6. Zoledronic Acid, magnesium salt (RN: 157432-59-2).
7. Zoledronic Acid, zinc salt (RN:157432-58-I).
U.S. Pat. No. 4,939,130 describes that the zoledronic acid obtained has a melting point of 239° C.
Particularly, in the request of patent US Serial No. 2005/0054616 diverse crystalline forms are described for the free acid and its sodium salts.
Seven crystalline forms of zoledronic acid are described in this document, identified as forms I, II, XII, XV, XVIII, XX and XXVI through their diffractograms of X-rays and TGA (Thermogravimetric Analysis).
The use of methansulphonic acid as a solvent in the preparation of alendronic acid and its salts is described in U.S. Pat. No. 4,922,007 (1990) and EP 462663 (1991).